Pterygium is an invasive and proliferative disease of the human ocular surface particularly prevalent in sun-exposed individuals. Histological examinations have identified foci of connective tissue elastosis and regions of severely damaged Bowman's membrane, suggesting either direct damage due to solar radiation or indirect damage due to excessive proteolytic activity. Pterygia are characterised by an inflammatory infiltrate, composed of neutrophils, mast cells, and lymphocytes, and can present with a prominent vascular reaction likely to be exacerbated by excessive cytokine and growth factor production by resident cells as well as infiltrating inflammatory cells.
Pterygium appears as a wedge-shaped fibrovascular growth of conjunctiva (the white of the eye) that extends onto the cornea. Whilst benign lesions, pterygia may become inflamed, may create instability of the pre-corneal tear film creating a symptomatic dry eye, may induce irregular cornea warpage and/or may obscure the visual axis. The standard therapeutic treatment for such pterygia involves surgical removal.
Surgical removal of pterygia involves ocular anaesthesia, patient sedation, and operative surgical pterygium removal where the pterygium is dissected away from ocular tissue. Pterygia have the propensity to regrow following their surgical removal. In an attempt to prevent regrowth of the pterygium, an ocular surgeon may remove some of the surface tissue of affected eye and suture it into the bead of the excised pterygium. Alternatively, an anti-metabolite such as mitomyacin C may be applied to the site of pterygium removal. Amano et al (B. R. J. Ophthalmol., 2000: 84, 618-621) described pterygium recurrence in patients who underwent pterygium surgery with associated mitomyacin C or β-irradiation treatment to reduce pterygium regrowth. In a retrospective study of 164 patients pterygium regrowth following mitomyacin C or β-irradiation treatment was respectively 8.74% and 23%. Topical antipoliferatives used in the eye for the treatment of lesions, such as to prevent pterygium regrowth, are ocularly corrosive. Complications of topical ocular mitomyacin C include corneoscleral melting, cataract and secondary glaucoma (Rubinfeld et al, Ophthalmology, 1992, 99: 1647-1654). β-irradiation to reduce pterygium regrowth has been associated with scleral necrosis and secondary infections (MacKenzie et al, Ophthalmology, 1991: 98, 1776-1781).
Recurrent pterygium following surgery are often more aggressive than the original pterygium showing aggressive fibrovascular growth (Chen et al, Am. J. Ophthalmol. 1995: 120, 151-160).
Thus, notwithstanding surgical removal of pterygium, with its attendant costs and risk of complications, pterygium regrow. The treatments to prevent pterygium are associated with side effects, and do not prevent pterygium regrowth in many cases.
Pinguecula is a benign, yellowish brown proliferative growth that forms on the conjunctiva. Pinguecula may cause irritation and scratchiness of the eye, dry eye, inflammation of the conjunctiva and effect appearance of the eye. Inflamed pinguecula, which cause ocular irritation or become unsightly, may require surgical removal. However, the post-operation scar may be as cosmetically objectionable as the pinguecula and pinguecula regrowth may occur following surgical removal.
Ocular surface dysplasias of the eye, such as limbal epithelial dysplasia, are proliferative diseases which form lesions in the form of cellular masses on the surface of the eye. These lesions may cause eye irritation, obscure vision, disrupt the tear film and/or be cosmetically unsightly. Standard treatments of such dysplasias comprise surgical excision and/or topical mitomyacin C treatment. Problems of lesion recurrence and the corrosive nature of anti-proliferative agents, such as mitomyacin C, remain a problem for the treatment of ocular surface dysplasias.
Ocular neoplastic disorders, such as malignancies of the limbus and eyelids in humans and animals may cause ocular irritation, visual disturbance, disturbance of the tear film (with associated dry eye) and eye pain, particularly as the neoplastic lesion increases in size. Ocular neoplasms may lead to potentially fatal invasive carcinoma or eye loss. The standard treatment for ocular neoplastic disorders, such as squamous cell carcinoma of the limbus, intraepithelial neoplasia of the cornea and conjunctiva, involve surgical removal of the malignant lesion and adjunctive therapy including cryotherapy, radiotherapy, immunotherapy and topical cytostatic agents. Recurrence rates following surgical excision may be as high as 54% (Erie et al, “Conjunctival and corneal intraepithelial and invasive neoplasia”, Ophthalmology 1986, 93: 176-183). Topical cysostatic agents such as mitomyacin C and 5-fluorouracil may impair physiological corneal epithelial replacement (Heigle et al, “Treatment of recurrent conjunctival epithelial neoplasia with topical mitomyacin C” Am. J. Ophthalmol. 1997: 124, 397-399). Surgical treatments, together with use of cytostatic agents, cryotherapy or radiation remain unsatisfactory (Tabin et al, Ophthalmology 1996: 104, 485-492; Lee, A., Hirst, L., Survey of Ophthalmology, 1995: 39, No. 6, 429-450).
Neutrophic keratitis, fibrosis of conjunctive drainage blebs in glaucoma and viral disorders of the eye have no particularly satisfactory treatment.
Interferon a has been proposed for the treatment of limbal dysplasia (Maskin, S. L., Arch. Ophthalmol. 1994, 1112-1114-1146) and ocular squamous cell carcinoma. Similarly, retinoic acid has been proposed for the treatment of dysplasia of the corneal epithelium (Wright, P. Trans. Opthalmol. Soc. UK 1985, 104: 869-74). However, such treatments have low efficacy in preventing lesion resolution and/or lesion recurrence compared with surgical treatments and have not been developed for patient treatment.